"Gastrin" and "CCK" receptors on histamine- and somatostatin-containing cells from rabbit fundic mucosa--I. Characterization by means of agonists

Abstract

A previous study has suggested the presence of two distinct binding sites for gasrin and cholecystokinin (CCK) in isolated non-parietal cells from rabbit gastric mucosa: a receptor which binds CCK-8 and CCK-39 with a high affinity and a receptor which binds gastrin and CCK-8 with the same high affinity and CCK-39 with a lower affinity. To characterize these receptors, their ability to induce phosphoinositide breakdown was investigated. Gastrin (HG-17), CCK-39 and CCK-8 induced [3H]-inositol phosphate ([3H]InsP) accumulation from [3H]inositol prelabelled cells with a high potency (EC50: 0.3-2.7 nM) but CCK-8 exhibited a higher efficacy than HG-17 or CCK-39. HG-17, CCK-8 and CCK-39 induced a rapid accumulation of [3H]inositol monophosphate ([3H]InsP1), [3H]inositol bisphosphate ([3H]InsP2) and [3H]inositol trisphosphate ([3H]InsP3) but CCK-8 caused a two times higher accumulation than HG-17 or CCK-39. Histamine- and somatostatin-containing cells appeared to be located in this non-parietal cells population. HG-17, CCK-8 and CCK-39 dose-dependently induced histamine release with the following order of potency: HG-17 = CCK-8 (EC50 approximately 0.2 nM) greater than CCK-39 (EC50 approximately 4 nM). In addition, HG-17 exhibited the highest efficacy. HG-17, CCK-8 and CCK-39 enhanced somatostatin-like immunoreactivity (SLI) release with the following order of potency: CCK-8 (EC50 approximately 0.1 nM) = CCK-39 greater than HG-17 (EC50 approximately 10 nM); CCK-8 and CCK-39 exhibited the highest efficacy. These results led us to the following conclusions: (i) existence of a "gastrin-type" and of a "CCK-type" receptor mediating phosphoinositide breakdown in these gastric non-parietal cells. CCK-8 interacts with both receptor-types with the same affinity; (ii) the release of histamine from histamine-containing cells could be induced following "gastrin-type" receptors activation; (iii) somatostatin release from D-cells present in this non-parietal cells population could be induced following "CCK-type" receptors activation.